Nucleic acids such as siRNA (small interfering RNA), miRNA (micro RNA) and shRNA (short hairpin RNA or small hairpin RNA) expression vectors and antisense oligonucleotides induce sequence-specific gene silencing in vivo and are known as oligonucleotide therapeutics.
Among the oligonucleotide therapeutics, siRNAs have attracted particular attention. siRNAs are double-stranded RNAs consisting of 19 to 23 base pairs and induce sequence-specific gene silencing called RNA interference (RNAi).
siRNAs are chemically stable; however, siRNAs have issues in therapeutic applications such as being liable to be decomposed by RNase (ribonuclease) in plasma and being unlikely to pass through the cell membrane alone (for example, see Patent Literature 1).
In order to address the above issues, it has been known that by encapsulating siRNA in a fine particle containing a cationic lipid, the encapsulated siRNA is protected from decomposition in blood plasma and can penetrate a lipophilic cell membrane (for example, see Patent Literature 1).
Patent Literature 2 to 5 disclose cationic lipids where are used for delivery of oligonucleotide therapeutics such as siRNAs and which have improved biodegradability.
Fine particles containing cationic lipids have such an issue of stability that the particles are likely to aggregate during storage, and a method for preventing aggregation by adding polyethylene glycol-modified lipids (PEG lipids) to the fine particles is known.
Further, Patent Literature 6 discloses a method for preventing aggregation and improving a delivery efficiency of nucleic acids by configuring fine particles that comprise a specific PEG lipid, which is PEG-DPG, and a preparation that comprises the fine particles and a deionized solvent.